The program described in this proposal is aimed at generating a more complete understanding of murine Ia antigens, with the eventual goal of determining what role these molecules play in the regulation of immune responses. This research will focus on genetic and chemical facets of Ia antigens that determine their structure, cell surface expression, and perhaps functions. Specifically, the following problems will be explored: 1. Polypeptide chain structure of native molecules; 2. Genetic organization of loci coding for Ia antigens; 3. Selective association of Ia polypeptide chains; 4. Regulation of cell surface expression of Ia polypeptide chains; 5. Structure-function relationships of Ia antigens. A variety of approaches will be used in this work, including two-dimensional polyacrylamide gel electrophoresis, peptide mapping, somatic cell genetics, and biochemical procedures.